Human Gene GCG (ENST00000418842.7_7) from GENCODE V47lift37
  Description: glucagon (from RefSeq NM_002054.5)
Gencode Transcript: ENST00000418842.7_7
Gencode Gene: ENSG00000115263.15_9
Transcript (Including UTRs)
   Position: hg19 chr2:162,999,392-163,008,757 Size: 9,366 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg19 chr2:162,999,874-163,005,688 Size: 5,815 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:162,999,392-163,008,757)mRNA (may differ from genome)Protein (180 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GLUC_HUMAN
DESCRIPTION: RecName: Full=Glucagon; Contains: RecName: Full=Glicentin; Contains: RecName: Full=Glicentin-related polypeptide; Short=GRPP; Contains: RecName: Full=Oxyntomodulin; Short=OXM; Short=OXY; Contains: RecName: Full=Glucagon; Contains: RecName: Full=Glucagon-like peptide 1; Short=GLP-1; AltName: Full=Incretin hormone; Contains: RecName: Full=Glucagon-like peptide 1(7-37); Short=GLP-1(7-37); Contains: RecName: Full=Glucagon-like peptide 1(7-36); Short=GLP-1(7-36); Contains: RecName: Full=Glucagon-like peptide 2; Short=GLP-2; Flags: Precursor;
FUNCTION: Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.
FUNCTION: GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis.
FUNCTION: GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.
FUNCTION: Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.
FUNCTION: Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Glucagon is secreted in the A cells of the islets of Langerhans. GLP-1, GLP-2, oxyntomodulin and glicentin are secreted from enteroendocrine cells throughout the gastrointestinal tract. GLP-1 and GLP-2 are also secreted in selected neurons in the brain.
INDUCTION: Glucagon release is stimulated by hypoglycemia and inhibited by hyperglycemia, insulin, and somatostatin. GLP-1 and GLP-2 are induced in response to nutrient ingestion.
PTM: Proglucagon is post-translationally processed in a tissue- specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and oxyntomodulin. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas.
PHARMACEUTICAL: Available under the names Glucagon (Eli Lilly) and GlucaGen or Glucagon Novo Nordisk (Novo Nordisk). Used to treat severe hypoglycemia in insulin-dependent diabetics.
MISCELLANEOUS: In the glucagon antagonist, His-53 and Phe-58 are missing. This antagonist has been successfully utilized to reduce glucose concentration in vivo.
SIMILARITY: Belongs to the glucagon family.
WEB RESOURCE: Name=Glucagon at Eli Lilly; Note=Clinical information on Eli Lilly glucagon products; URL="http://www.lillyDiabetes.com/Products/PatientInfo.cfm";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: GCG
Diseases sorted by gene-association score: hyperglycemia (16), hypoglycemia (14), dumping syndrome (13), short bowel syndrome (11), diabetes mellitus, insulin-dependent (6), insulinoma (5), obesity (5), glucose intolerance (5), abnormality of glucagon secretion (4), diabetes mellitus, noninsulin-dependent (4), intestinal disease (3), diabetes mellitus, insulin-dependent, 21 (3), bartter syndrome, type 1 (3), gastrointestinal system disease (2), maturity-onset diabetes of the young (2), endocrine gland cancer (2), pancreas disease (2), glucose metabolism disease (2), endocrine pancreas disease (2), acquired metabolic disease (2), erythematosquamous dermatosis (2), blind loop syndrome (2), acute insulin response (2), primary optic atrophy (2), overnutrition (2), diabetes mellitus, insulin-dependent, 15 (1), median arcuate ligament syndrome (1), glycogen storage disease iiia (1), meninges sarcoma (1), pancreatic cholera (1), small intestine leiomyosarcoma (1), small intestinal sarcoma (1), glycogen storage disease vi (1), fructose-1,6-bisphosphatase deficiency (1), gastric leiomyoma (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 162.28 RPKM in Pancreas
Total median expression: 207.87 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -21.2099-0.214 Picture PostScript Text
3' UTR -82.10482-0.170 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR015550 - Glucagon-like
IPR000532 - Glucagon_GIP_secretin_VIP

Pfam Domains:
PF00123 - Peptide hormone

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1BH0 - X-ray 1D0R - NMR 1NAU - NMR 2G49 - X-ray MuPIT 2L63 - NMR 2L64 - NMR 3IOL - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P01275
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005102 receptor binding
GO:0005179 hormone activity
GO:0005515 protein binding
GO:0031769 glucagon receptor binding
GO:0042802 identical protein binding

Biological Process:
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway
GO:0007189 adenylate cyclase-activating G-protein coupled receptor signaling pathway
GO:0007631 feeding behavior
GO:0008283 cell proliferation
GO:0010469 regulation of receptor activity
GO:0010737 protein kinase A signaling
GO:0010800 positive regulation of peptidyl-threonine phosphorylation
GO:0032092 positive regulation of protein binding
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0035948 positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter
GO:0042594 response to starvation
GO:0043066 negative regulation of apoptotic process
GO:0045860 positive regulation of protein kinase activity
GO:0050796 regulation of insulin secretion
GO:0051571 positive regulation of histone H3-K4 methylation
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071377 cellular response to glucagon stimulus
GO:0090280 positive regulation of calcium ion import
GO:1900118 negative regulation of execution phase of apoptosis

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005788 endoplasmic reticulum lumen
GO:0034774 secretory granule lumen


-  Descriptions from all associated GenBank mRNAs
  J04040 - Human glucagon mRNA, complete cds.
BC005278 - Homo sapiens glucagon, mRNA (cDNA clone MGC:12325 IMAGE:3950435), complete cds.
JD263438 - Sequence 244462 from Patent EP1572962.
JD241570 - Sequence 222594 from Patent EP1572962.
JD237736 - Sequence 218760 from Patent EP1572962.
JD553512 - Sequence 534536 from Patent EP1572962.
JD302712 - Sequence 283736 from Patent EP1572962.
JD160190 - Sequence 141214 from Patent EP1572962.
JD073489 - Sequence 54513 from Patent EP1572962.
BT006813 - Homo sapiens glucagon mRNA, complete cds.
DQ892521 - Synthetic construct clone IMAGE:100005151; FLH187121.01X; RZPDo839D1272D glucagon (GCG) gene, encodes complete protein.
DQ895732 - Synthetic construct Homo sapiens clone IMAGE:100010192; FLH187117.01L; RZPDo839D1262D glucagon (GCG) gene, encodes complete protein.
KJ891227 - Synthetic construct Homo sapiens clone ccsbBroadEn_00621 GCG gene, encodes complete protein.
X05388 - Human pancreas mRNA for glucagon (exon 2).
X05386 - Human pancreas mRNA for glucagon (exon 1 fragment).

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P01275 (Reactome details) participates in the following event(s):

R-HSA-163625 Glucagon binds to Glucagon receptor
R-HSA-400459 Signal peptidase hydrolyzes preproGLP-1 to proGLP-1
R-HSA-420123 Glucagon-like receptor 2 binds GLP2
R-HSA-744886 The Ligand:GPCR:Gs complex dissociates
R-HSA-749452 The Ligand:GPCR:Gq complex dissociates
R-HSA-381612 Glucagon-like Peptide-1 Receptor (GLP1R) binds Glucagon-like peptide-1
R-HSA-9023632 DPP4(39-766) hydrolyzes Glucagon-like Peptide-1 (GLP-1)
R-HSA-9023633 DPP4(1-766) hydrolyzes Glucagon-like Peptide-1 (GLP-1)
R-HSA-749448 Liganded Gq-activating GPCRs bind inactive heterotrimeric Gq
R-HSA-744887 Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs
R-HSA-825631 Glucagon:GCGR mediates GTP-GDP exchange
R-HSA-379048 Liganded Gq/11-activating GPCRs act as GEFs for Gq/11
R-HSA-379044 Liganded Gs-activating GPCR acts as a GEF for Gs
R-HSA-381706 GLP-1R:GLP-1 activates G(s)
R-HSA-163359 Glucagon signaling in metabolic regulation
R-HSA-420092 Glucagon-type ligand receptors
R-HSA-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-418555 G alpha (s) signalling events
R-HSA-416476 G alpha (q) signalling events
R-HSA-163685 Energy Metabolism
R-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-400508 Incretin synthesis, secretion, and inactivation
R-HSA-388396 GPCR downstream signalling
R-HSA-1430728 Metabolism
R-HSA-500792 GPCR ligand binding
R-HSA-422356 Regulation of insulin secretion
R-HSA-2980736 Peptide hormone metabolism
R-HSA-372790 Signaling by GPCR
R-HSA-392499 Metabolism of proteins
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A6NN65, ENST00000418842.1, ENST00000418842.2, ENST00000418842.3, ENST00000418842.4, ENST00000418842.5, ENST00000418842.6, GCG , GLUC_HUMAN, NM_002054, P01275, Q53TP6, uc319okx.1, uc319okx.2
UCSC ID: ENST00000418842.7_7
RefSeq Accession: NM_002054.5
Protein: P01275 (aka GLUC_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.